Cytokinesis

Cytokinesis is the final step of cell division in which the cytoplasm of a parent cell is divided to form two daughter cells. It is crucial for maintaining genomic stability and proper cellular function. Errors in cytokinesis can lead to aneuploidy, tissue dysfunction, or tumor development.

Definition and Overview

Cytokinesis refers to the process by which a single eukaryotic cell physically separates into two distinct daughter cells following mitosis or meiosis. While mitosis and meiosis focus on the segregation of chromosomes, cytokinesis ensures that the cytoplasm, organelles, and cell membrane are equally divided, allowing the formation of fully functional cells.

• Definition: Physical division of the cytoplasm and cellular contents following nuclear division.
• Distinction from mitosis and meiosis: Cytokinesis occurs after chromosomal segregation, completing the cell cycle.
• Biological significance: Essential for organismal growth, tissue repair, and proper distribution of organelles and molecules between daughter cells.

Mechanisms of Cytokinesis

Animal Cell Cytokinesis

In animal cells, cytokinesis involves the formation of a contractile ring that pinches the cell into two:

• Contractile ring: Composed of actin filaments and myosin II, positioned at the equatorial plane.
• Cleavage furrow formation: Ingression of the plasma membrane driven by contraction of the actomyosin ring.
• Progression: Ring contraction continues until the two daughter cells are fully separated.

Plant Cell Cytokinesis

Plant cells use a different mechanism due to the rigid cell wall:

• Cell plate formation: Vesicles carrying cell wall materials coalesce at the center of the dividing cell to form a new wall.
• Phragmoplast: A microtubule-based structure that guides vesicles to the division site.
• Vesicle trafficking and fusion: Ensures proper assembly of the new plasma membrane and cell wall between daughter cells.

Fungal and Protist Cytokinesis

Fungi and protists display diverse cytokinetic mechanisms:

• Septum formation: Fungi often form a septum that separates daughter cells.
• Contractile or cortical cleavage: Some protists use a contractile ring or cortical constriction similar to animal cells.
• Variations: Mechanisms depend on species-specific cellular architecture and environmental conditions.

Molecular Regulation

Key Proteins and Complexes

Cytokinesis is regulated by multiple proteins that coordinate the assembly and contraction of the division machinery:

• Rho GTPases: Act as molecular switches to control actin filament formation and contractile ring assembly.
• Actin and myosin networks: Form the contractile apparatus that drives cleavage furrow ingression in animal cells.
• Centralspindlin and anillin: Stabilize the contractile ring and link it to the plasma membrane, ensuring accurate cell division.

Signaling Pathways

Several signaling cascades ensure cytokinesis occurs in coordination with the cell cycle:

• Mitotic exit network (MEN): Controls exit from mitosis and initiation of cytokinesis in yeast and other eukaryotic cells.
• Septation initiation network (SIN): Regulates septum formation and contractile ring assembly, particularly in fungi.
• Cell cycle checkpoints: Monitor chromosome segregation and spindle integrity to prevent cytokinesis before proper chromosomal separation.

Coordination with the Cell Cycle

Cytokinesis is tightly integrated with the progression of the cell cycle to ensure accurate cell division:

• Occurs during late anaphase and telophase, after chromosomes have been segregated.
• Interaction with the mitotic spindle ensures correct positioning of the contractile apparatus at the cell equator.
• Checkpoints prevent initiation of cytokinesis in the presence of misaligned chromosomes, thereby preserving genomic stability.

Clinical and Biological Relevance

Proper cytokinesis is essential for tissue development, maintenance, and cellular homeostasis. Disruptions in cytokinesis can lead to various clinical and biological consequences:

• Cancer: Failure of cytokinesis can result in aneuploidy and polyploidy, contributing to tumorigenesis and tumor progression.
• Developmental disorders: Defective cell division during embryogenesis may cause congenital anomalies or impaired organ development.
• Therapeutic targets: Proteins and pathways regulating cytokinesis, such as Rho GTPases and centralspindlin, are being explored for targeted cancer therapies.

Experimental Techniques to Study Cytokinesis

Various laboratory methods are used to investigate the mechanisms and regulation of cytokinesis:

• Live-cell imaging: Time-lapse microscopy allows visualization of contractile ring formation and cleavage furrow ingression in real time.
• Fluorescence microscopy: Fluorescent markers and probes highlight cytoskeletal components, signaling molecules, and membrane dynamics.
• Molecular and genetic manipulation: Knockdown or knockout of key cytokinesis regulators using siRNA or CRISPR-Cas9 helps determine their functional roles.
• Biochemical assays: In vitro reconstitution of actin-myosin networks and measurement of contractile forces provide mechanistic insights.

Recent Advances and Research Directions

Recent studies have provided deeper insights into the molecular and cellular mechanisms of cytokinesis, revealing new regulatory pathways and potential therapeutic targets:

• High-resolution microscopy has enabled visualization of contractile ring dynamics and vesicle trafficking at unprecedented detail.
• Mechanistic studies have identified additional proteins and complexes involved in actin filament organization, membrane remodeling, and spindle positioning.
• Comparative studies across species have highlighted evolutionary conservation and divergence in cytokinetic mechanisms, providing insight into fundamental cellular processes.
• Research into cytokinesis failure in cancer and other proliferative disorders is guiding the development of novel therapeutic strategies targeting division-specific proteins.

References

1. Glotzer M. The molecular requirements for cytokinesis. Science. 2005;307(5716):1735-1739.
2. Green RA, Paluch E, Oegema K. Cytokinesis in animal cells. Annu Rev Cell Dev Biol. 2012;28:29-58.
3. Pollard TD. Mechanics of cytokinesis in eukaryotes. Curr Opin Cell Biol. 2010;22(1):50-56.
4. Mishima M. Central spindle assembly and cytokinesis. Cell Mol Life Sci. 2008;65(14):1925-1943.
5. Rappaport R. Cytokinesis in animal cells. Cambridge: Cambridge University Press; 1996.
6. Glotzer M. Cytokinesis: a view from the contractile ring. Curr Biol. 2009;19(14):R631-R633.
7. Adams RR, Carmena M, Earnshaw WC. Chromosomal passengers and the regulation of mitosis. Nat Rev Mol Cell Biol. 2001;2(10):797-808.
8. Eggert US, Mitchison TJ, Field CM. Animal cytokinesis: from parts list to mechanisms. Annu Rev Biochem. 2006;75:543-566.